Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis.,Cell Death & Disease

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Spatiotemporal coordination of trophoblast and allantoic Rbpj signaling directs normal placental morphogenesis.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-06-05 , DOI: 10.1038/s41419-019-1683-1
Jinhua Lu _{1,

2} , Weiwei Wu ₃ , Qiliang Xin ₄ , Chan Zhou ₄ , Jianqi Wang _{1,

2} , Zhangli Ni ₄ , Dong Liu _{1,

2} , Yingchun Xu _{1,

2} , Yongqin Yu _{1,

2} , Ningjie Yang _{1,

2} , Yang Sun _{1,

2} , Bo He _{1,

2} , Shuangbo Kong _{1,

2} , Shumin Wang ₅ , Chao Wang ₄ , Haibin Wang _{1,

2}

Affiliation

The placenta, responsible for the nutrient and gas exchange between the mother and fetus, is pivotal for successful pregnancy. It has been shown that Rbpj, the core transcriptional mediator of Notch signaling pathway, is required for normal placentation in mice. However, it remains largely unclear how Rbpj signaling in different placental compartments coordinates with other important regulators to ensure normal placental morphogenesis. In this study, we found that systemic deletion of Rbpj led to abnormal chorioallantoic morphogenesis and defective trophoblast differentiation in the ectoplacental cone (EPC). Employing mouse models with selective deletion of Rbpj in the allantois versus trophoblast, combining tetraploid aggregation assay, we demonstrated that allantois-expressed Rbpj is essential for chorioallantoic attachment and subsequent invagination of allantoic blood vessels into the chorionic ectoderm. Further studies uncovered that allantoic Rbpj regulates chorioallantoic fusion and morphogenesis via targeting Vcam1 in a Notch-dependent manner. Meanwhile, we also revealed that trophoblast-expressed Rbpj in EPC facilitates Mash2's transcriptional activity, promoting the specification of Tpbpα-positive trophoblasts, which differentiate into trophoblast subtypes responsible for interstitial and endovascular invasion at the later stage of placental development. Collectively, our study further shed light on the molecular network governing placental development and functions, highlighting the necessity of a spatiotemporal coordination of Rbpj signaling for normal placental morphogenesis.

中文翻译：

滋养细胞和尿囊Rbpj信号的时空协调指导正常的胎盘形态发生。

胎盘负责母亲与胎儿之间的营养和气体交换，对于成功怀孕至关重要。已经显示，Notch信号传导途径的核心转录介质Rbpj是小鼠正常胎盘发育所必需的。然而，在很大程度上尚不清楚不同胎盘区室中的Rbpj信号如何与其他重要的调节因子协调以确保正常的胎盘形态发生。在这项研究中，我们发现Rbpj的系统性删除导致在外胎盘锥体（EPC）中绒毛膜尿囊形态发生异常和滋养细胞分化缺陷。运用四倍体聚集测定法，在尿囊和滋养细胞中选择删除Rbpj的小鼠模型，我们证明了尿囊素表达的Rbpj对于绒毛膜尿囊附件和随后的尿囊血管向绒毛膜外胚层的内陷至关重要。进一步的研究发现，尿囊素Rbpj通过以Notch依赖的方式靶向Vcam1来调节绒毛尿囊融合和形态发生。同时，我们还揭示了在EPC中表达滋养层的Rbpj促进了Mash2的转录活性，促进了Tpbpα阳性滋养层的规格，后者在胎盘发育的后期分化为负责间隙和血管内侵袭的滋养层亚型。总的来说，我们的研究进一步阐明了控制胎盘发育和功能的分子网络，

更新日期：2019-06-05

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